Background: Cardiovascular (CV) events are the leading cause of death in prostate cancer. Men with prostate cancer are likely to have CV risk factors and CV-related concomitant medications. In the phase 3 HERO study, a 54% lower incidence of major adverse cardiac events was reported in men treated with the oral GnRH receptor antagonist relugolix vs leuprolide. Herein, we characterize the impact of concomitant CV therapies on efficacy and safety in the HERO study. Methods: In HERO, 930 men with advanced prostate cancer were randomized 2:1 and treated with relugolix (120 mg orally once daily [after single 360 mg loading dose] or leuprolide (injections every 3 months) for 48 weeks. Subgroups analyzed included men who received antihypertensives, antithrombotics, or lipid-modifying therapies, as well as the most common drug classes (>10%) and single most common agent within each class. Assessments included sustained testosterone suppression to castrate levels (<50 ng/dL) through 48 weeks and safety parameters (adverse events). Results: Antihypertensives, antithrombotics, and lipid modifying agents were utilized by 52.7%, 39.1%, and 39.6% of men in the HERO trial, respectively (table). In the main subgroups, point estimates for sustained castration rates were consistent with the overall estimates of relugolix and leuprolide observed in the overall population (table). Sustained castration rates were also consistent for men taking the most common drug classes (table) and individual agents in each class (losartan [n=103]: relugolix, 95.4% vs. leuprolide, 80.6%; amlodipine [n=229]: 97.2% vs. 85.5%; metoprolol [n=88]: 95.7% vs. 86.9%; acetylsalicylic acid [n=259]: 97.0% vs. 92.1%; clopidogrel [n=43]: 96.4% vs. 86.7%; simvastatin [n=78]: 98.0% vs. 87.3%). Incidence and types of adverse events were similar among men who received antihypertensives, antithrombotics, and lipid modifying agents during the trial. Conclusions: In the HERO trial, relugolix suppressed testosterone and was generally well tolerated when given with concomitant CV agents, with results consistent with those of the overall population. Clinical trial information: NCT03085095.

ADP=Adenosine diphosphate; COX= Cyclooxygenase.*Cumulative probability of testosterone to <50 ng/dL through 48 weeks.